Process for the synthesis of hydroxy aromatic acids

ABSTRACT

Hydroxy aromatic acids are produced in high yields and high purity (&gt;95%) from halogenated aromatic acids in a reaction mixture containing a copper source and a ligand that coordinates to copper.

This application is a division of and claims the benefit of U.S.application Ser. No. 11/604,941, filed Nov. 28, 2006, which by thisreference is incorporated in its entirety as a part hereof for allpurposes.

TECHNICAL FIELD

This invention relates to the manufacture of hydroxy aromatic acids,which are valuable for a variety of purposes such as use asintermediates or as monomers to make polymers.

BACKGROUND

Hydroxy aromatic acids are useful as intermediates and additives in themanufacture of many valuable materials including pharmaceuticals andcompounds active in crop protection, and are also useful as monomers inthe production of polymers. Salicylic acid (o-hydroxybenzoic acid), forexample, is used in the manufacture of aspirin and has otherpharmaceutical applications. Esters of p-hydroxybenzoic acid, known as“parabens”, are used as food and cosmetic preservatives.P-hydroxybenzoic acid and 6-hydroxy-2-naphthoic acid are each used as acomponent of liquid crystalline polymers.

Various preparations of hydroxybenzoic acids, including2,5-dihydroxyterephthalic acid (“DHTA”), are known. Marzin, in Journalfuer Praktische Chemie, 1933, 138, 103-106, teaches the synthesis of2,5-dihydroxyterephthalic acid (“DHTA”) from 2,5-dibromoterephthalicacid (“DBTA”) in the presence of copper powder.

Singh et al, in Jour. Indian Chem. Soc., Vol. 34, No. 4, pages 321˜323(1957), report the preparation of a product that includes DHTA by thecondensation of DBTA with phenol in the presence of KOH and copperpowder.

Rusonik et al, Dalton Trans., 2003, 2024-2028, describe thetransformation of 2-bromobenzoic acid into salicylic acid, benzoic acid,and diphenoic acid in a reaction catalyzed by Cu(I) in the presence ofvarious ligands. A tertiary tetraamine minimizes the formation ofdiphenoic acid in use with Cu(I).

Comdom et al, Synthetic Communications, 32(13), 2055-59 (2002), describea process for the synthesis of salicylic acids from 2-chlorobenzoicacids. Stoichiometric amounts of pyridine (0.5 to 2.0 moles per mole of2-chlorobenzoic acid) are used such as at least 1.0 mole pyridine permole 2-chlorobenzoic acid. Cu powder is used as a catalyst along withthe pyridine.

Gelmont et al, Organic Process Research & Development, 6(5), 591-596(2002), and U.S. Pat. No. 5,703,274, describe a process for thepreparation of 5-hydroxyisophthalic acid by hydrolyzing5-bromoisophthalic acid, mixtures of 5-bromoisophthalic acid,dibromoisophthalic acid isomers, and salts thereof in an aqueousalkaline solution in the presence of a copper catalyst at a temperatureof 100 to 270° C.

Israeli Patent 112,706 discloses a process for the preparation of4-hydroxyphthalic acid, and a mixture of 3- and 4-hydroxyphthalic acids,by hydrolyzing the corresponding bromophthalic acids in an aqueousalkaline solution in the presence of a copper catalyst at a temperatureof 100 to 160° C. Examples of copper catalysts disclosed include Cu(0),CuCl, CuCl₂, Cu₂O, CuO, CuBr₂, CuSO₄, Cu(OH)₂, and copper (II) acetate.

The various prior art processes for making hydroxybenzoic acids arecharacterized by long reaction times, limited conversion resulting insignificant productivity loss, or the need to run under pressure and/orat higher temperatures (typically 140 to 250° C.) to get reasonablerates and productivity. A need therefore remains for a process by whichhydroxybenzoic acids can be produced economically; with low inherentoperational difficulty; and with high yields and high productivity insmall- and large-scale operation, and in batch and continuous operation.

SUMMARY

One embodiment of this invention provides a process for preparing ahydroxy aromatic acid that is described generally by the structure ofFormula I(COOH)_(m)—Ar—(OH)_(n)  Iwherein Ar is a C₆˜C₂₀ arylene radical, n and m are each independently anonzero value, and n+m is less than or equal to 8, by (a) contacting ahalogenated aromatic acid that is described generally by the structureof Formula II,(COOH)_(m)—Ar—(X)_(n)  IIwherein each X is independently Cl, Br or I, and Ar, n and m are as setforth above, with a base in water to form therefrom the correspondingm-basic salt of the halogenated aromatic acid in water; (b) contactingthe m-basic salt of the halogenated aromatic acid with a base in water,and with a copper source in the presence of a ligand that coordinates tocopper, to form the m-basic salt of a hydroxy aromatic acid from them-basic salt of the halogenated aromatic acid at a solution pH of atleast about 8; (c) optionally, separating the m-basic salt of thehydroxy aromatic acid from the reaction mixture in which it is formed;and (d) contacting the m-basic salt of the hydroxy aromatic acid withacid to form therefrom a n-hydroxy aromatic acid.

Yet another embodiment of this invention provides a process forpreparing an

n-alkoxy aromatic acid by preparing an

n-hydroxy aromatic acid in the manner described above and thenconverting the n-hydroxy aromatic acid to an n-alkoxy aromatic acid.

Yet another embodiment of this invention consequently provides a processfor preparing an n-alkoxy aromatic acid that is described generally bythe structure of Formula VI(COOH)_(m)—Ar—(OR⁹)_(n)  VIwherein Ar is a C₆˜C₂₀ arylene radical, each R⁹ is independently asubstituted or unsubstituted C₁₋₁₀ alkyl group, n and m are eachindependently a nonzero value, and n+m is less than or equal to 8, by(a) contacting a halogenated aromatic acid that is described generallyby the structure of Formula II,(COOH)_(m)—Ar—(X)_(n)  IIwherein each X is independently Cl, Br or I, and Ar, n and m are as setforth above, with a base in water to form therefrom the correspondingm-basic salt of the halogenated aromatic acid in water; (b) contactingthe m-basic salt of the halogenated aromatic acid with a base in water,and with a copper source in the presence of a ligand that coordinates tocopper, to form the m-basic salt of a hydroxy aromatic acid from them-basic salt of the halogenated aromatic acid at a solution pH of atleast about 8; (c) optionally, separating the m-basic salt of thehydroxy aromatic acid from the reaction mixture in which it is formed;(d) contacting the m-basic salt of the hydroxy aromatic acid with acidto form therefrom an n-hydroxy aromatic acid that is described generallyby the structure of Formula I,(COOH)_(m)—Ar—(OH)_(n)  Iwherein Ar, n and m are as set forth above; and (e) converting then-hydroxy aromatic acid to an n-alkoxy aromatic acid that is describedgenerally by the structure of Formula VI, wherein Ar, R⁹, n and m are asset forth above.

Yet another embodiment of this invention provides a process forpreparing a 2,5-dihydroxyterephthalic acid or a 2,5-dialkoxyterephthalicacid as described above that further includes a step of subjecting the2,5-dihydroxyterephthalic acid or the 2,5-dialkoxyterephthalic acid to areaction to prepare therefrom a compound, monomer, oligomer or polymer.

Yet another embodiment of this invention consequently provides a processfor preparing a compound, monomer, oligomer or polymer by preparing ahydroxy aromatic acid that is described generally by the structure ofFormula I(COOH)_(m)—Ar—(OH)_(n)  Iwherein Ar is a C₆˜C₂₀ arylene radical, n and m are each independently anonzero value, and n+m is less than or equal to 8, by (a) contacting ahalogenated aromatic acid that is described generally by the structureof Formula II,(COOH)_(m)—Ar—(X)_(n)  IIwherein each X is independently Cl, Br or I, and Ar, n and m are as setforth above, with a base in water to form therefrom the correspondingm-basic salt of the halogenated aromatic acid in water; (b) contactingthe m-basic salt of the halogenated aromatic acid with a base in water,and with a copper source in the presence of a ligand that coordinates tocopper, to form the m-basic salt of a hydroxy aromatic acid from them-basic salt of the halogenated aromatic acid at a solution pH of atleast about 8; (c) optionally, separating the m-basic salt of thehydroxy aromatic acid from the reaction mixture in which it is formed;(d) contacting the m-basic salt of the hydroxy aromatic acid with acidto form therefrom an n-hydroxy aromatic acid; (e) optionally, convertingthe n-hydroxy aromatic acid to a n-alkoxy aromatic acid; and (f)subjecting the n-hydroxy aromatic acid and/or the n-alkoxy aromatic acidto a reaction to prepare therefrom a compound, monomer, oligomer orpolymer.

In yet another embodiment, the ligand in one or more of the processesdescribed herein may be a diketone.

DETAILED DESCRIPTION

This invention provides a high yield and high productivity process forpreparing a hydroxy aromatic acid as described generally by thestructure of Formula I(COOH)_(m)—Ar—(OH)_(n)  Iby contacting a halogenated aromatic acid as described generally by thestructure of Formula II(COOH)_(m)—Ar—(X)_(n)  IIwith base to form the m-basic salt of the halogenated aromatic acid;contacting the m-basic salt of the halogenated aromatic acid with base,and with a copper source in the presence of a ligand that coordinates tocopper, to form the m-basic salt of an n-hydroxy aromatic acid; and thencontacting the dibasic salt of the n-hydroxy aromatic acid with acid toform the n-hydroxy aromatic acid product.

In both Formulae I and II, Ar is a C₆˜C₂₀ arylene radical, n and m areeach independently a nonzero value, and n+m is less than or equal to 8;and in Formula II, each X is independently Cl, Br or I. The aryleneradical denoted by “—Ar—” is a multi-valent aromatic radical formed bythe removal of two or more hydrogens from different carbon atoms on thearomatic ring, or on the aromatic rings when the structure ismulticyclic. There is consequently, for example, the possibility in thearylene radical that hydrogens may be removed from two up to all sixcarbon atoms on a benzyl ring, or hydrogens may be removed from any twoand up to eight positions on either one or both rings of a naphthylradical.

The arylene radical, “Ar”, may be substituted or unsubstituted. Thearylene radical, when unsubstituted, is a univalent group containingonly carbon and hydrogen. In the arylene radical, however, one or more 0or S atoms may optionally be substituted for any one or more of thein-chain or in-ring carbon atoms, provided that the resulting structurecontains no —O—O— or —S—S— moieties, and provided that no carbon atom isbonded to more than one heteroatom. One example of a suitable aryleneradical is phenylene, as shown below.

An “m-basic salt”, as the term is used herein, is the salt formed froman acid that contains in each molecule m acid groups having areplaceable hydrogen atom.

Various halogenated aromatic acids, to be used as a starting material inthe process of this invention, are commercially available. For example,2-bromobenzoic acid is available from Aldrich Chemical Company(Milwaukee, Wis.). It can be synthesized, however, by oxidation ofbromomethylbenzene as described in Sasson et al, Journal of OrganicChemistry (1986), 51(15), 2880-2883. Other halogenated aromatic acidsthat can be used include without limitation 2,5-dibromobenzoic acid,2-bromo-5-nitrobenzoic acid, 2-bromo-5-methylbenzoic acid,2-chlorobenzoic acid, 2,5-dichlorobenzoic acid,2-chloro-3,5-dinitrobenzoic acid, 2-chloro-5-methylbenzoic acid,2-bromo-5-methoxybenzoic acid, 5-bromo-2-chlorobenzoic acid,2,3-dichlorobenzoic acid, 2-chloro-4-nitrobenzoic acid,2,5-dichloroterephthalic acid, and 2-chloro-5-nitrobenzoic acid, all ofwhich are commercially available.

Other halogenated aromatic acids useful as a starting material in theprocess of this invention include those shown in the left column of thetable below, wherein X=Cl, Br or I, and wherein the correspondinghydroxy aromatic acid produced therefrom by the process of thisinvention is shown in the right column:

I II (COOH)_(m)—Ar—(X)_(n) (COOH)_(m)—Ar—(OH)_(n)

In step (a), a halogenated aromatic acid is contacted with base in waterto form therefrom the corresponding m-basic salt of the halogenatedaromatic acid. In step (b), the m-basic salt of the halogenated aromaticacid is contacted with base in water, and with a copper source in thepresence of a ligand that coordinates to copper, to form the m-basicsalt of a hydroxy aromatic acid from the m-basic salt of the halogenatedaromatic acid.

The base used in step (a) and/or step (b) may be an ionic base, and mayin particular be one or more of a hydroxide, carbonate, bicarbonate,phosphate or hydrogen phosphate of one or more of Li, Na, K, Mg or Ca.The base used may be water-soluble, partially water-soluble, or thesolubility of the base may increase as the reaction progresses and/or asthe base is consumed. NaOH and Na₂CO₃ are preferred, but other suitableorganic bases may be selected, for example, from the group consisting oftrialkylamines (such as tributylamine);N,N,N′,N′-tetramethylethylenediamine; and N-alkyl imidazoles (forexample, N-methylimidazole). In principle any base capable ofmaintaining a pH above 8 and/or binding the acid produced during thereaction of the halogenated aromatic acid is suitable.

The specific amounts of base to be used in steps (a) and/or (b) dependon the strength of the base. In step (a), a halogenated aromatic acid ispreferably contacted with at least about m equivalents of water-solublebase per equivalent of halogenated aromatic acid. One “equivalent” asused for a base in this context is the number of moles of base that willreact with one mole of hydrogen ions; for an acid, one equivalent is thenumber of moles of acid that will supply one mole of hydrogen ions.

In step (b), enough base should be used to maintain a solution pH of atleast about 8, or at least about 9, or at least about 10, and preferablybetween about 9 and about 11. Thus, typically in step (b), the dibasicsalt of the halogenated aromatic acid is contacted with at least about nequivalents of base, such as a water-soluble base, per equivalent of them-basic salt of the halogenated aromatic acid.

In alternative embodiments, however, it may be desirable in steps (a)and (b) to use a total of at least about n+m+1 equivalents of base, suchas a water-soluble base, in the reaction mixture per equivalent of thehalogenated aromatic acid originally used at the start of the reaction.A base used in an amount as described above is typically a strong base,and is typically added at ambient temperature. The base used in step (b)may be the same as, or different than, the base used in step (a).

As mentioned above, in step (b), the m-basic salt of the halogenatedaromatic acid is also contacted with a copper source in the presence ofa ligand that coordinates to copper. The copper source and the ligandmay be added sequentially to the reaction mixture, or may be combinedseparately (for example, in a solution of water or acetonitrile) andadded together. The copper source may be combined with the ligand in thepresence of oxygen in water, or be combined with a solvent mixturecontaining water.

From the presence together in the reaction mixture of the copper sourceand the ligand, in a basic solution of the m-basic salt of thehalogenated aromatic acid, there is obtained an aqueous mixturecontaining the m-basic salt of a hydroxy aromatic acid, copperspecie(s), the ligand, and a halide salt. If desired, the m-basic saltof the hydroxy aromatic acid may, at this stage and before theacidification in step (d), be separated from the mixture [as optionalstep (c)], and may be used as an m-basic salt in another reaction or forother purposes.

The m-basic salt of the hydroxy aromatic acid is then contacted in step(d) with acid to convert it to the hydroxy aromatic acid product. Anyacid of sufficient strength to protonate the m-basic salt is suitable.Examples include without limitation hydrochloric acid, sulfuric acid andphosphoric acid.

The reaction temperature for steps (a) and (b) is preferably betweenabout 60 and about 120° C., more preferably between about 75 and about95° C.; and the process thus in various embodiments involves a step ofheating the reaction mixture. The solution is typically allowed to coolbefore the acidification in step (d) is carried out. In variousembodiments, oxygen may be excluded during the reaction.

The copper source is copper metal [“Cu(0)”], one or more coppercompounds, or a mixture of copper metal and one or more coppercompounds. The copper compound may be a Cu(I) salt, a Cu(II) salt, ormixtures thereof. Examples include without limitation CuCl, CuBr, CuI,Cu₂SO₄, CuNO₃, CuCl₂, CuBr₂, CuI₂, CuSO₄, and Cu(NO₃)₂. The selection ofthe copper source may be made in relation to the identity of thehalogenated aromatic acid used. For example, if the starting halogenatedaromatic acid is a bromobenzoic acid, CuCl, CuBr, CuI, Cu₂SO₄, CuNO₃,CuCl₂, CuBr₂, CuI₂, CuSO₄, and Cu(NO₃)₂ will be included among theuseful choices. If the starting halogenated aromatic acid is achlorobenzoic acid, CuBr, CuI, CuBr₂ and CuI₂ will be included among theuseful choices. CuBr and CuBr₂ are in general preferred choices for mostsystems. The amount of copper used is typically about 0.1 to about 5 mol% based on moles of halogenated aromatic acid.

When the copper source is Cu(0), Cu(0), copper bromide and a ligand maybe combined in the presence of air. In the case of Cu(0) or Cu(I), apredetermined amount of metal and ligand may be combined in water, andthe resulting mixture may be reacted with air or dilute oxygen until acolored solution is formed. The resulting metal/ligand solution is addedto the reaction mixture containing the m-basic salt of the halogenatedaromatic acid and base in water.

The ligand may be a diketone described generally by Formula IV

wherein A is

R¹ and R² are each independently selected from substituted andunsubstituted C₁-C₁₆ n-alkyl, iso-alkyl and tertiary alkyl groups; andsubstituted and unsubstituted C₆-C₃₀ aryl and heteroaryl groups;

R³ is selected from H; substituted and unsubstituted C₁-C₁₆ n-alkyl,iso-alkyl and tertiary alkyl groups; substituted and unsubstitutedC₆-C₃₀ aryl and heteroaryl groups; and a halogen;

R⁴, R⁵, R⁶ and R⁷ are each independently H or a substituted orunsubstituted C₁-C₁₆ n-alkyl, iso-alkyl or tertiary alkyl group; and

n=0 or 1.

The term “unsubstituted”, as used with reference to an alkyl or arylgroup in a diketone as described above, means that the alkyl or arylgroup contains no atoms other than carbon and hydrogen. In a substitutedalkyl or aryl group, however, one or more 0 or S atoms may optionally besubstituted for any one or more of the in-chain or in-ring carbon atoms,provided that the resulting structure contains no —O—O— or —S—S—moieties, and provided that no carbon atom is bonded to more than oneheteroatom. n a preferred embodiment, R³ is H.

In one embodiment, a diketone suitable for use herein as the ligand is2,2′,6,6′-tetramethylheptanedione-3,5 (Formula V):

Other diketones suitable for use herein as the ligand include, withoutlimitation, 2,4-pentanedione and 2,3-pentanedione.

A ligand suitable for use herein may be selected as any one or more orall of the members of the whole population of ligands described by nameor structure above. A suitable ligand may, however, also be selected asany one or more or all of the members of a subgroup of the wholepopulation, where the subgroup may be any size (1, 2, 6, 10 or 20, forexample), and where the subgroup is formed by omitting any one or moreof the members of the whole population as described above. As a result,the ligand may in such instance not only be selected as one or more orall of the members of any subgroup of any size that may be formed fromthe whole population of ligands as described above, but the ligand mayalso be selected in the absence of the members that have been omittedfrom the whole population to form the subgroup.

In various embodiments, the ligand may be provided in an amount of about1 to about 10, preferably about 1 to about 2, molar equivalents ofligand per mole of copper. As used herein, the term “molar equivalent”indicates the number of moles of ligand that will interact with one moleof copper.

When the halogenated aromatic acid is a brominated aromatic acid, thecopper source may be Cu(0) and/or a Cu(I) salt, and it may be combinedwith the ligand in the presence of oxygen in water, or a solvent mixturecontaining water. Alternatively, when the Cu(I) salt is CuBr, and theligand is one of the diketones named specifically above (such as2,2′,6,6′-tetramethylheptanedione-3,5), the ligand may be provided in anamount of two molar equivalents per mole of copper, and the CuBr may becombined with the ligand in the presence of water and air.

The ligand is believed to facilitate the action of the copper source asa catalyst, and/or the copper source and the ligand are believed tofunction together to act as a catalyst, to improve one or moreattributes of the reaction.

The process described above also allows for effective and efficientsynthesis of related compounds, such as n-alkoxy aromatic acids, whichmay be described generally by the structure of Formula VI:(COOH)_(m)—Ar—(OR⁹)_(n)  VIwherein Ar, m and n are described as set forth above, and each R⁹ isindependently a substituted or unsubstituted C₁₋₁₀ alkyl group. An R⁹is, when unsubstituted, a univalent group containing only carbon andhydrogen. In any such alkyl group, however, one or more O or S atoms mayoptionally be substituted for any one or more of the in-chain carbonatoms, provided that the resulting structure contains no —O—O— or —S—S—moieties, and provided that no carbon atom is bonded to more than oneheteroatom.

An n-hydroxy aromatic acid, as prepared by the process of thisinvention, may be converted to an n-alkoxy aromatic acid, and suchconversion may be accomplished, for example, by contacting the hydroxyaromatic acid under basic conditions with an n-alkyl sulfate of theformula (R⁹)_(n)SO₄. One suitable method of running such a conversionreaction is as described in Austrian Patent No. 265,244. Suitable basicconditions for such conversion are a solution pH of at least about 8, orat least about 9, or at least about 10, and preferably about 9 to about11, using one or more bases such as described above.

In certain embodiments, it may be desired to separate the n-hydroxyaromatic acid from the reaction mixture in which it was formed beforeconverting it to an n-alkoxy aromatic acid.

The process described above also allows for effective and efficientsynthesis of products made from the resulting 2,5-dihydroxyterephthalicacid or 2,5-dialkoxyterephthalic acid such as a compound, a monomer, oran oligomer or polymer thereof. These produced materials may have one ormore of ester functionality, ether functionality, amide functionality,imide functionality, imidazole functionality, carbonate functionality,acrylate functionality, epoxide functionality, urethane functionality,acetal functionality, and anhydride functionality.

Representative reactions involving a material made by the process ofthis invention, or a derivative of such material, include, for example,making a polyester from a 2,5-dihydroxyterephthalic acid and eitherdiethylene glycol or triethylene glycol in the presence of 0.1% ofZN₃(BO₃)₂ in 1-methylnaphthalene under nitrogen, as disclosed in U.S.Pat. No. 3,047,536 (which is incorporated in its entirety as a parthereof for all purposes). Similarly, a 2,5-dihydroxyterephthalic acid isdisclosed as suitable for copolymerization with a dibasic acid and aglycol to prepare a heat-stabilized polyester in U.S. Pat. No. 3,227,680(which is incorporated in its entirety as a part hereof for allpurposes), wherein representative conditions involve forming aprepolymer in the presence of titanium tetraisopropoxide in butanol at200˜250° C., followed by solid-phase polymerization at 280° C. at apressure of 0.08 mm Hg.

A 2,5-dihydroxyterephthalic acid has also been polymerized with thetrihydrochloride-monohydrate of tetraaminopyridine in strongpolyphosphoric acid under slow heating above 100° C. up to about 180° C.under reduced pressure, followed by precipitation in water, as disclosedin U.S. Pat. No. 5,674,969 (which is incorporated in its entirety as apart hereof for all purposes); or by mixing the monomers at atemperature from about 50° C. to about 110° C., and then 145° C. to forman oligomer, and then reacting the oligomer at a temperature of about160° C. to about 250° C. as disclosed in U.S. Provisional ApplicationNo. 60/665,737, filed Mar. 28, 2005 (which is incorporated in itsentirety as a part hereof for all purposes), published as WO2006/104974. The polymer that may be so produced may be apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer such as apoly(1,4-(2,5-dihydroxy)phenylene-2,6-pyrido[2, 3-d:5,6-d′]bisimidazole)polymer, or apoly[(1,4-dihydrodiimidazo[4,5-b:4′,5′-e]pyridine-2,6-diyl)(2,5-dihydroxy-1,4-phenylene)]polymer. The pyridobisimidazole portionthereof may, however, be replaced by any or more of a benzobisimidazole,benzobisthiazole, benzobisoxazole, pyridobisthiazole and apyridobisoxazole; and the 2,5-dihydroxy-p-phenylene portion thereof maybe replace the derivative of one or more of isophthalic acid,terephthalic acid, 2,5-pyridine dicarboxylic acid, 2,6-naphthalenedicarboxylic acid, 4,4′-diphenyl dicarboxylic acid, 2,6-quinolinedicarboxylic acid, and 2,6-bis(4-carboxyphenyl) pyridobisimidazole.

EXAMPLES

The present invention is further defined in the following examples. Itshould be understood that these examples, while indicating preferredembodiments of the invention, are given by way of illustration only.From the above discussion and these examples, one skilled in the art canascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various uses andconditions.

Materials: The following materials were used in the examples. Allreagents were used as received. Product purity was determined by ¹H NMR.

The 2-bromobenzoic acid (97% purity),2,2′,6,6′-tetramethylheptanedione-3,5 (>98% purity), 2,4-pentanedione(99+% purity) and 2,3-pentanedione (97% purity) were obtained fromAldrich Chemical Company (Milwaukee, Wis., USA).

Copper(II) sulfate (“CuSO₄”) (98% purity) was obtained from StremChemicals, Inc. (Newburyport, Mass., USA). Copper(I)bromide (“CuBr”)(98%) and copper (II) bromide (“CuBr₂”) were obtained from AcrosOrganics (Geel, Belgium). Na₂CO₃ (99.5%) was obtained from EM Science(Gibbstown, N.J.).

As used herein, the term “conversion” refers to how much reactant wasused up as a fraction or percentage of the theoretical amount. The term“selectivity” for a product P refers to the molar fraction or molarpercentage of P in the final product mix. The conversion multiplied bythe selectivity thus equals the maximum “yield” of P; the actual or“net” yield will normally be somewhat less than this because of samplelosses incurred in the course of activities such as isolating, handling,drying, and the like. The term “purity” denotes what percentage of thein-hand, isolated sample is actually the specified substance.

The term “35% HCl” as used in the Examples denotes aqueous hydrochloricacid whose concentration is 35 grams of HCl per 100 mL of solution. Themeaning of abbreviations is as follows “h” means hour(s), “mL” meansmilliliter(s), “mmol” means millimole(s), “NMR” means nuclear magneticresonance spectroscopy, “CONV” means conversion (percent), “SEL” meansselectivity (percent), “T” means temperature, and “t” means time.

Example 1

This example demonstrates the formation of 2,5-dihydroxyterephthalicacid from 2,5-dibromoterephthalic acid using CuBr and the diketoneligand 2,2′,6,6′-tetramethylheptanedione-3,5 (as shown in Formula V):

Under nitrogen, 2.00 g (6.2 mmol) of 2,5-dibromoterephthalic acid wascombined with 15 g of H₂O; 0.679 g (6.4 mmol) of Na₂CO₃ was then added.The mixture was heated to reflux with stirring for 30 min, remainingunder a nitrogen atmosphere. Another 0.940 g (9.0 mmol) of Na₂CO₃ wasadded to the reaction mixture and reflux was continued for 30 min.Separately, 9 mg (0.06 mmol)(0.01 mol equiv) of CuBr and 25 mg (0.14mmol)(0.02 mol equiv) of 2,2′,6,6′-tetramethylheptanedione-3,5 werecombined with 2 mL H₂O under nitrogen. The resulting mixture was stirredunder an air atmosphere until the CuBr was dissolved. This solution wasadded to the stirred reaction mixture via syringe at 80° C. undernitrogen and stirred for 30 h at 80° C. After cooling to 25° C., thereaction mixture was acidified with HCl (conc.), producing a dark yellowprecipitate. The yellow precipitate was filtered and washed with water.After drying, a total of 1.26 g of crude 2,5-dihydroxyterephthalic acidand 2-hydroxyterephthalic acid was collected. The purity of2,5-dihydroxyterephthalic acid was determined by ¹H NMR to be about 89%.The net yield of 2,5-dihydroxyterephthalic acid was determined to be92%.

Example 2

Under nitrogen, 2.01 g (10 mmol) of 2-bromobenzoic acid was combinedwith 10 g of H₂O; 1.32 g (12.5 mmol) of Na₂CO₃ was then added. Themixture was heated to reflux with stirring for 60 min, remaining under anitrogen atmosphere. Separately, 67 mg (0.3 mmol)(0.03 mol equiv) ofCuBr₂ and 63 mg (0.0.6 mmol) (0.6 mol equiv) of 2,4-pentanedione werecombined with 2 mL H₂O under nitrogen. This solution was added to thestirred reaction mixture via syringe at 80° C. under nitrogen andstirred for 27 h at 80° C. After cooling to 25° C., the reaction mixturewas acidified with HCl (conc.), producing an off-white precipitate. Theprecipitate was filtered, washed with water and dried. Both theconversion and selectivity of salicylic acid were determined to be 98%by ¹H NMR. The net yield was determined to be 96%.

Example 3

Under nitrogen, 2.01 g (10 mmol) of 2-bromobenzoic acid was combinedwith 10 g of H₂O; 1.32 g (12.5 mmol) of Na₂CO₃ was then added. Themixture was heated to reflux with stirring for 60 min, remaining under anitrogen atmosphere. Separately, 67 mg (0.3 mmol)(0.03 mol equiv) ofCuBr₂ and 66 mg (0.0.6 mmol) (0.6 mol equiv) of 2,3-pentanedione werecombined with 2 mL H₂O under nitrogen. This solution was added to thestirred reaction mixture via syringe at 80° C. under nitrogen andstirred for 16 h at 80° C. After cooling to 25° C., the reaction mixturewas acidified with HCl (conc.), producing an off-white precipitate. Theprecipitate was filtered, washed with water and dried. The conversionand selectivity of salicylic acid were determined to be 100% and 94%,respectively, by ¹H NMR. The net yield was determined to be 94%.

Where an embodiment of this invention is stated or described ascomprising, including, containing, having, being composed of or beingconstituted by certain features, it is to be understood, unless thestatement or description explicitly provides to the contrary, that oneor more features in addition to those explicitly stated or described maybe present in the embodiment. An alternative embodiment of thisinvention, however, may be stated or described as consisting essentiallyof certain features, in which embodiment features that would materiallyalter the principle of operation or the distinguishing characteristicsof the embodiment are not present therein. A further alternativeembodiment of this invention may be stated or described as consisting ofcertain features, in which embodiment, or in insubstantial variationsthereof, only the features specifically stated or described are present.

Where the indefinite article “a” or “an” is used with respect to astatement or description of the presence of a step in a process of thisinvention, it is to be understood, unless the statement or descriptionexplicitly provides to the contrary, that the use of such indefinitearticle does not limit the presence of the step in the process to one innumber.

Where a range of numerical values is recited herein, unless otherwisestated, the range is intended to include the endpoints thereof, and allintegers and fractions within the range. It is not intended that thescope of the invention be limited to the specific values recited whendefining a range.

1. A process for preparing an n-alkoxy aromatic acid from a hydroxyaromatic acid that is described generally by the structure of Formula I(COOH)_(m)—Ar—(OH)_(n)  I wherein Ar is a C₆˜C₂₀ arylene radical, n andm are each independently a nonzero value, and n+m is less than or equalto 8, comprising the steps of (a) contacting a halogenated aromatic acidthat is described generally by the structure of Formula II,(COOH)_(m)—Ar—(X)_(n)  II  wherein each X is independently Cl, Br or I,and Ar, n and m are as set forth above, with a base in water to formtherefrom the corresponding m-basic salt of the halogenated aromaticacid in water; (b) contacting the m-basic salt of the halogenatedaromatic acid with a base in water, and with a copper source in thepresence of a ligand that coordinates to copper, to form the in-basicsalt of a hydroxy aromatic acid from the in-basic salt of thehalogenated aromatic acid at a solution pH of at least about 8, whereinthe ligand comprises a diketone described generally by Formula IV

 wherein A is

R¹ and R² are each independently selected from substituted andunsubstituted C₁-C₁₆ n-alkyl, iso-alkyl and tertiary alkyl groups; andsubstituted and unsubstituted C₆-C₃₀ aryl and heteroaryl groups; R³ isselected from H; substituted and unsubstituted C₁-C₁₆ n-alkyl, iso-alkyland tertiary alkyl groups; substituted and unsubstituted C₆-C₃₀ aryl andheteroaryl groups; and a halogen; R₄, R₅, R₆ and R₇ are eachindependently H or a substituted or unsubstituted C₁-C₁₆ n-alkyl,iso-alkyl or tertiary alkyl group; and n=0 or 1; (c) optionally,separating the m-basic salt of the hydroxy aromatic acid from thereaction mixture in which it is formed; (d) contacting the in-basic saltof the hydroxy aromatic acid with acid to form therefrom an n-hydroxyaromatic acid; and (e) converting the n-hydroxy aromatic acid to ann-alkoxy aromatic acid.
 2. A process according to claim 1 wherein then-hydroxy aromatic acid is contacted under basic conditions with adialkyl sulfate of the formula R⁹R¹⁰ SO₄ wherein R⁹ and R¹⁰ are eachindependently a substituted or unsubstituted C₁₋₁₀ alkyl group.
 3. Aprocess for preparing a compound, monomer, oligomer or polymer from ahydroxy aromatic acid that is described generally by the structure ofFormula I(COOH)_(m)—Ar—(OH)_(n)  I wherein Ar is a C₆˜C₂₀ arylene radical, n andm are each independently a nonzero value, and n+m is less than or equalto 8, comprising the steps of (a) contacting a halogenated aromatic acidthat is described generally by the structure of Formula II,(COOH)_(m)—Ar—(X)_(n)  II  wherein each X is independently Cl, Br or I,and Ar, n and m are as set forth above, with a base in water to formtherefrom the corresponding m-basic salt of the halogenated aromaticacid in water; (b) contacting the in-basic salt of the halogenatedaromatic acid with a base in water, and with a copper source in thepresence of a ligand that coordinates to copper, to form the in-basicsalt of a hydroxy aromatic acid from the in-basic salt of thehalogenated aromatic acid at a solution pH of at least about 8, whereinthe ligand comprises a diketone described generally by Formula IV

 wherein A is

R¹ and R² are each independently selected from substituted andunsubstituted C₁-C₁₆ n-alkyl, iso-alkyl and tertiary alkyl groups; andsubstituted and unsubstituted C₆-C₃₀ aryl and heteroaryl groups; R³ isselected from H; substituted and unsubstituted C₁-C₁₆ n-alkyl, iso-alkyland tertiary alkyl groups; substituted and unsubstituted C₆-C₃₀ aryl andheteroaryl groups; and a halogen; R⁴, R⁵, R⁶ and R⁷ are eachindependently H or a substituted or unsubstituted C₁-C₁₆ n-alkyl,iso-alkyl or tertiary alkyl group; and  n=0 or 1; (c) optionally,separating the m-basic salt of the hydroxy aromatic acid from thereaction mixture in which it is formed; (d) contacting the in-basic saltof the hydroxy aromatic acid with acid to form therefrom an n-hydroxyaromatic acid; and (e) subjecting the n-hydroxy aromatic acid to areaction to prepare therefrom a compound, monomer, oligomer or polymer.4. A process according to claim 3 wherein a polymer prepared comprises apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene)polymer.
 5. Aprocess according to claim 1 further comprising a step of subjecting then-alkoxy aromatic acid to a reaction to prepare therefrom a compound,monomer, oligomer or polymer.
 6. A process according to claim 1 wherein,in steps (a) and (b), a total of about n+m+1 normal equivalents ofwater-soluble base are added to the reaction mixture per equivalent ofthe halogenated aromatic acid.
 7. A process according to claim 1 whereinthe copper source comprises Cu(0), a Cu(I) salt, a Cu(II) salt, or amixture thereof.
 8. A process according to claim 1 wherein the coppersource is selected from the group consisting of CuCl, CuBr, CuI, Cu₂SO₄,CuNO₃, CuCl₂, CuBr₂, CuI₂, CuSO₄, Cu(NO₃)₂, and mixtures thereof.
 9. Aprocess according to claim 1 wherein the ligand is 2,4-pentanedione,2,3-pentanedione or 2,2′,6,6′-tetramethylheptanedione-3,5 (as shownbelow):


10. A process according to claim 1 wherein a base comprises one or moreof a water-soluble hydroxide, phosphate, carbonate, or bicarbonate ofone or more of Li, Na, K, Mg, or Ca.
 11. A process according to claim 1wherein copper is provided in an amount of between about 0.1 and about 5mol % based on moles of halogenated aromatic acid.
 12. A processaccording to claim 1 wherein the ligand is provided in an amount ofbetween about one and about two molar equivalents per mole of copper.13. A process according to claim 3 wherein, in steps (a) and (b), atotal of about n+m+1 normal equivalents of water-soluble base are addedto the reaction mixture per equivalent of the halogenated aromatic acid.14. A process according to claim 3 wherein the copper source comprisesCu(0), a Cu(I) salt, a Cu(II) salt, or a mixture thereof.
 15. A processaccording to claim 3 wherein the copper source is selected from thegroup consisting of CuCl, CuBr, CuI, Cu₂SO₄, CuNO₃, CuCl₂, CuBr₂, CuI₂,CuSO₄, Cu(NO₃)₂, and mixtures thereof.
 16. A process according to claim3 wherein R³ is H.
 17. A process according to claim 3 wherein the ligandis 2,4-pentanedione, 2,3-pentanedione or2,2′,6,6′-tetramethylheptanedione-3,5 (as shown below):


18. A process according to claim 3 wherein a base comprises one or moreof a water-soluble hydroxide, phosphate, carbonate, or bicarbonate ofone or more of Li, Na, K, Mg, or Ca.
 19. A process according to claim 3wherein copper is provided in an amount of between about 0.1 and about 5mol % based on moles of halogenated aromatic acid.
 20. A processaccording to claim 3 wherein the ligand is provided in an amount ofbetween about one and about two molar equivalents per mole of copper.